Description: The administrative component of this PSO (PPG) will have both scientific and organizational responsibilities. This Program Project will involve four interrelated research projects supported by two core facilities. Dr. Breakefield will serve as the Program Director and liaison between laboratories. She will be assisted in administrative responsibilities by an experienced Grants manager, Ms. Robin Sobolewski. Dr. Breakefield will make all final decisions on the operations ofthe PSO after extensive discussions with involved individuals. Dr. Breakefield will be advised by an Internal Advisory Committee consisting of three senior members of the PPG: Dr. Pradeep Bhide, Dr. David Standaert and Dr. Laurie Ozelius, as well as two investigators at Partners (MGH/BWH) with related expertise - Dr. James Gusella (human genetics and neurologic disease) and Dr. David Kwiatkowski (mouse models for neurologic disease and cell biology). Combination conference calls/onsite meetings will be held at least twice a year with this group as issues arise needing advice. This group will also be present at the External Advisory meeting. The functions of this committee will consist of critical review of key data, strategic guidance in planning future experiments and collaborations, advice on any conflicts that arise within the PPG group or with collaborators, and appropriate adjustments resulting from any changes in Pl status or their locations. Patient issues will be handled by the physician/scientists in the group, Drs. Nutan Sharma and David Standaert, as well as our collaborator. Dr. Susan Bressman, with genetic counseling issues covered by Drs. Sharma and Bressman, with assistance from Ms. Trisha Multhaupt-Buell, a Genetic Counselor in the Movement Disorder Clinic. Advice on research strategy and evaluation of progress will be undertaken in consultation with a standing External Advisory Committee on a yearly basis at a day-long meeting at MGH. This committee will consist of five individuals (two, James Gusella and David Kwiatkowski also serving as members ofthe Internal Advisory Committee) with combined expertise in human genetics, neuronal development, cell biology, mouse models and clinical aspects of dystonia. (According to NINDS guidelines the additional names of members of the committee and letters from them will be provided when the application is funded). A detailed progress report incorporating critiques from the external review prepared by the External Advisors and Internal non-PPG Advisors will be distributed to all investigators in the Center and incorporated into the progress report of the non-competitive continuation applications.